Using field-effect transistor (FET)-based biosensors created from nanowires (NWs) and carbon nanotubes (CNTs), researchers have demonstrated detection of cancer biomarkers from nM to fM range in serum, in vitro detection of nM proteins in cell growth systems, and quanitification of the affinities/kinetics of the protein interactions with fM-level sensitivities. The fM-level limit-of-detection (LOD) achieved by such nanoscale FET biosensors for monitoring biomarker concentrations would enable label-free, single-molecule-level detection of trace-level amount biomarkers. The arrays of such biosensors with consistent transistor responses would serve as reliable lab-on-a-chip platforms for precisely determining the kinetics of various biomolecule interactions. However, serious constraints imposed on nanofabrication severely prohibit the reliable manufacturing of the affordable biosensor chips utilizing such one dimensional (1D) nanostructures. In particular, high-quality, small-size NWs and CNTs are needed to make biosensors with fM-level LOD for concentration monitoring (or single-molecule-level LOD for trace-level amount detection). Especially, for trace-level amount detection, the critical dimensions of the sensing channels need to be comparable to the impact dimensions of charged molecules to maximize the gating effect due to the charged molecules and achieve very low LOD. CNTs and many NWs are usually produced by using bottom-up synthesis methods (e.g., chemical, vapor deposition CVD)). The community currently lacks proper top-down planar nanofabrication processes to produce ordered arrays of such nanostructures, which makes it very challenging to realize parallel high-throughput assay using biosensors made from these nanostructures. High-quality Si NW biosensor arrays can be made using top-down lithographic techniques. However, the fabrication of such Si NW arrays usually needs expensive semiconductor-on-insulator (SOI) substrates and exquisite nanolithographic tools, which can result in a high processing cost and is not very suitable for manufacturing affordable (even disposable) assay chips for practical clinical biosensing applications.
Emerging two-dimensional (2D) atomically layered materials, such as graphene, topological insulators (Tis), and transition metal dichalcogenides (TMDCs), recently attracted a great deal of interest because of their attractive electronic/optoelectronic properties, large abundance, and compatibility to planar nanofabrication processes. Due to their atomically thin structures, the transport properties of 2D layers are highly sensitive to the external stimuli, which can enable new ultrasensitive 2D FETs suitable for biosensing applications. Especially, in comparison with the thin film transistors made from conventional bulk semiconductors (e.g., Si and III-V compounds), the transistors based on molybdenum disulfide (MoS2) and other atomically layered semiconductors are expected to exhibit much more sensitive electrical responses to antigen-antibody binding events. Furthermore, all 2D layers have an extremely low density of dangling bonds on their surfaces, which can result in high-quality FET channels with low densities of scattering centers (and hence low Flicker noise level), and enable highly sensitive, low-noise level detecting of biomolecules.
In contrast to zero-bandgap graphene, semiconducting TMDCs have sizable bandgaps. Therefore, TMDC-based FETs exhibit high On/Off current ratios up to 108, which, in combination with their atomically thin structures, can potentially enable the higher detection sensitivities for gas, chemical, and biological sensing applications. Therefore, it is very promising to realize cost-efficient manufacturing of multiplexing assays based on TMDC transistor arrays in the future.
Toward such envisaged bio-assay capability, additional device-oriented research is needed for quantitatively calibrating the sensor responses measured from multiple sets of TMDC FET biosensors, so that the calibrated response signals are consistent with each other and can synergistically enable precise quantification of biomarker concentrations (or amounts) as well as the affinities/kinetics of biomolecule interactions.
This section provides background information related to the present disclosure which is not necessarily prior art.